Data from PIK3CA Mutations in <i>In situ</i> and Invasive Breast Carcinomas

Abstract

<div>Abstract<p>The PIK3 signaling pathway has been identified as one of the most important and most frequently mutated pathways in breast cancer. Somatic mutations in the catalytic subunit of <i>PIK3CA</i> have been found in a significant fraction of breast carcinomas, and it has been proposed that mutant <i>PIK3CA</i> plays a role in tumor initiation. However, the majority of primary human tumors analyzed for genetic alterations in <i>PIK3CA</i> have been invasive breast carcinomas and the frequency of <i>PIK3CA</i> mutations in preinvasive lesions has not been explored. To investigate this, we sequenced exons 9 and 20 of <i>PIK3CA</i> in pure ductal carcinoma <i>in situ</i> (DCIS), DCIS adjacent to invasive carcinoma, and invasive ductal breast carcinomas. In a subset of cases, both <i>in situ</i> and invasive areas were analyzed from the same tumor. We found that the frequency of <i>PIK3CA</i> mutations was essentially the same (∼30%) in all three histologic groups. In some cases, <i>in situ</i> and invasive areas of the same tumor were discordant for PIK3CA status, and in two cases in which multiple invasive and adjacent <i>in situ</i> areas within the same tumor were analyzed independently, we detected intratumor heterogeneity for <i>PIK3CA</i> mutations. Our results suggest that mutation of <i>PIK3CA</i> is an early event in breast cancer that is more likely to play a role in breast tumor initiation than in invasive progression, although a potential role for exon 9 mutations in the progression of a subset of DCIS cases cannot be excluded. Cancer Res; 70(14); 5674–8. ©2010 AACR.</p></div>